Nootropics and Smart Drugs Formulations with Ultrasonics

Smart drugs and nootropic supplements are consumed as “cognitive enhancers” in order to increase cognitive function, brain capacity, concentration, memory and creativity, to boost motivation and mental energy as well as to support brain health. To promote the transport of the bioactive compounds such as nootropics, smart drugs and energizing substances across the blood-brain-barrier (BBB), the molecules should be in a nano-enhanced form. Ultrasonically prepared nano-liposomes, micelles, solid-lipid nanoparticles, nanostructured nano carriers and nano-emulsions are known to increase the bioavailability of bioactive molecules, vitamins and phytochemicals.

Nootropics or smart drugs are brain and body stimulating molecules – so-called cognitive enhancers – , which can be distinguished into the following categories racetams, stimulants, adaptogens, cholinergics, serotonergics, dopaminergics, metabolic function smart drugs and more categories.
Interested in those different categories of nootropics? Click here to read more about nootropics and their categorization!

What are Liposomes and Lipid-Based Nanocarriers?

Liposomes and lipid-based nano carriers such as nano-emulsions, nano-suspensions, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are known as potent drug carrier systems, which delivery bioactive molecules and nutrients to the targeted cell site and result thereby in superior bioavailability and absorption rates.

Liposomes

Liposomes can be categorized as a specific form of nanostructured lipid nanocarriers. Liposomes are spherical vesicles with an aqueous core enclosed by one or more lipid bilayers. Since liposomes offer the capability of encapsulate lipophilic and hydrophilic molecules, they have gained profound acceptance as a highly potent drug delivery system. In its self-assembled, self-closed structure, a liposome can encapsulate multiple bioactive compounds (i.e. nutrients or therapeutic molecules) at once. Its phospholipidic bilayer protects the entrapped bioactive molecules against hydrolysis and oxidative degradation. Since the structure of the liposome’s shell exhibits a significant similarity to mammalian cell, liposomes are capable to transfer bioactive compounds into cells and subcellular sites. Known advantages of liposomal delivery systems include their protections against enzymatic degradation, their low toxicity, high biocompatibility, biodegradability and non-immunogenicity.

Other Lipidic Nano-Carriers

Lipidic nano-carriers or lipid-based nano-carriers are defined as nano-sized drug / molecule delivery systems, which use lipid structures to encapsulate bioactive molecules in order to obtain improved bioavailability, higher absorption rates, enhanced long-term stability and protection against external degradation factors (e.g. oxidation, hydrolysis). Nanostructured lipid carriers include solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanoliposomes, micelles, nanoemulsions,nanosuspensions and lipid nanotubes. The specific chemical composition and its corresponding physicochemical characteristics give each nano-carrier form unique benefits, which make them suitable for specific administration forms (e.g. oral, intravenous, intranasal, transdermal etc.), molecule combinations, loading capacity or time-release formulations.
Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are defined as solid particles consisting of a lipid matrix in an aqueous phase stabilized by surfactants.
Liposomal and other nano-encapsulated (e.g. SLNs, NLCs) supplements offer a superior bioavailability, which means a very high percentage of the bioactive substance (e.g. vitamin, antioxidant, flavonoid etc.) is absorbed and metabolized by the body’s cells. Only a very small fraction is wasted since it is not absorbed but excreted by the body. This makes nano-liposomal formulations very potent, efficacious and reliable since nearly all of the bioactive molecules are delivered to the destination cells.

Ultrasonic Formulation of Stimulating Molecules with Highest Bioavailability

Ultrasonic nano-emulsification and nano-encapsulation makes nootropic and psychoactive molecules water-soluble and thereby highly absorbable and bioavailable. A higher absorption rate as well as increased bioavailability and biocompatibility make the bioactive substance more potent and may enable it to cross the blood-brain-barrier.

Ultrasonic Formulation of Nootropics

• Liposomes
• Nano-Emulsions
• Micelles
• Solid-Lipid Nanoparticles (SLN)
• Nanostructured Lipid Carriers (NLC)
• Inclusion Complex (e.g. cyclodextrin)
• Niosomes

There are manifold brain health and capacity supporting molecules, nutrients and phytochemicals, which can be extracted and/or formulated into nano-enhanced supplements, such as liquids, tinctures, capsules, nasal sprays, fortified food products etc.

Most known nootropics are substances of the racetam class, such as piracetam, aniracetam, oxiracetam, pramiracetam and phenylpiracetam. Many Racetams are lipophilic (=fat-soluble). Using ultrasonic treatment, the fat-soluble racetam is encapsulated in a nano-enhanced form such as nano-emulsions, liposomes, solid-lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). These nano-enhanced formulations turn the water-repellant, fat-soluble racetam into a water-soluble product. Since the blood stream in the human body is water-based nano-enhanced water-soluble formulations offer a significantly higher bioavailability.

Ultrasonically Nano-Enhanced Smart Drugs

The ultrasonic encapsulation and nano-formulation technology enables for the preparation of highly bioavailable supplements and therapeutics. Bioactive molecules which benefit from being ultrasonically formulated into a liposomal or other nano-structured lipid carrier system include vitamins, antioxidants, flavonoids, botanical extracts, minerals, amino acids and peptides.

• Vitamins and antioxidants, which can be either extracted from a natural source or be synthesized, include vitamin C, B vitamins, glutathione, resveratrol, CoQ10 (ubiquinone), etc.
• Herbal and botanical molecules such as CBD, THC, CBG (cannabis), green tea catechins (e.g. EGCG), nicotine, caffeine, ashwagandha, berberine, kratom etc.
• Fungi / mushroom extracts such as astragalus, lion‘s mane, turkey tail, chaga, psilocybin (magic mushrooms), etc.
• Amino acids such as creatine, glycine, 5-HTP (5-hydroxytryptophan), phenylalanine, L-theanine (an amino acid analogue found in tea), GABA (gamma-aminobutyric acid), taurine, N-acetylcysteine (NAC), L-tyrosine, etc.
• Minerals such as magnesium chelates (e.g. magnesium threonate, magnesium orotate) can be ultrasonically encapsulated as nano-particulates into liposomes.
• Nutrients, peptides, and other molecules such as alpha-GPC, melatonin, choline (choline bitartrate, choline chloride), (racemic) ketamine, omega-3 fatty acids (EPA, DHA), α-lipoic acid (ALA), selegiline (L-deprenyl), centrophenoxine, oxytocin, methylene blue, etc.

The nano-enhanced liposomal formulation of bioactive molecules and nutrients offers a superior bioavailability and may enable the targeted substances to cross the blood brain barrier. The encapsulation prevents the bioactive molecules against acid-induced hydrolysis in the stomach and enzymatic degradation throughout the gastrointestinal tract, so that a high percentage of the nutrient is transported undamaged to the targeted site of cells.

Excursus: Ultrasonic Extraction of Phyto-Chemicals

Sonication is the superior technology to release bioactive molecules from plants, fungi and bacteria. Ultrasonic extraction is a non-thermal method, whose working principle is based on acoustic cavitation. Acoustic / ultrasonic cavitation creates mechanical shear and turbulences, which perforate and disrupt cell walls and membranes and promotes mass transfer. Thereby, sonication releases the bioactive substances from the cell interior and transfers it to the solvent (e.g. water, ethanol, glycerine, vegetable oil etc. ).
Learn more about ultrasonic extraction of bioactive molecules from botanicals!

High-Performance Ultrasonicators for Nootropic Formulations

Hielscher Ultrasonics’ systems are reliable machines used in the pharmaceutical and supplement production to formulate high-quality nootropics and smart drugs, which range from nano-emulsions to liposomes, nanostructured lipid carriers, solid-lipid nanoparticles, and inclusions complexes that are loaded with vitamins, antioxidants, flavonoids, peptides, polyphenols and other bioactive compounds and provide highest bioavailability, great stability and functionality. To meet its customers’ demands, Hielscher supplies ultrasonicators from the compact hand-held lab homogenizer and bench-top ultrasonicators to fully industrial ultrasonic systems for the production of high-volumes of nootropics and smart drug formulations. Ultrasonic formulating processes can be run as batch or as continuous inline process using an ultrasonic flow-through reactor. A broad range of ultrasonic sonotrodes (probes) and reactor vessels are available to ensure an optimal setup for your liposome production. The robustness of Hielscher’s ultrasonic equipment allows for 24/7 operation under heavy duty in demanding environments and ensure a long-life cycle of the ultrasonicators.
The precise control over all important process parameters such as amplitude, pressure, temperature and sonication time make the ultrasonic process reliable and reproducible. Hielscher Ultrasonics knows of the importance of continuously high product quality and supports supplement and therapeutics manufacturers to implement process standardisation and GMP (Good Manufacturing Practices) by intelligent software and automatic data recording. Our digital ultrasonic homogenizers automatically record all ultrasonic process parameters on a built-in SD-card. Digital touch displays and browser remote control allow for continuous process monitoring and enable to adjust the process parameters precisely whenever required. This facilitates process monitoring and quality control significantly.
The table below gives you an indication of the approximate processing capacity of our ultrasonicators: